Renal failure is a life-threatening and costly medical condition. End-stage renal disease, defined as severe renal dysfunction requiring chronic dialysis or kidney transplantation, is increasing in prevalence and has an annual mortality rate exceeding 20%. Less severe loss of renal function also has important health consequences. Mild to moderate reductions in renal function and microalbuminuria are important predictors of cardiovascular disease and death, in high-risk groups as well as in the general population. The risk of adverse outcomes increases with decreasing renal function. Even in the absence of known risk factors for renal function decline, such as hypertension or diabetes, kidney dysfunction may develop slowly over decades. Slowing or preventing decline in renal function may favorably impact morbidity and mortality. Genetic factors, biological processes (such as inflammation) and environmental factors (such as analgesic use) may contribute to renal function decline. Heightened activity of the renin-angiotensin system (RAS), particularly of angiotensin II, is an important mediator of renal pathophysiology. Thus, genes related to the RAS system may have important long-term effects on renal function. Chronic inflammation may adversely affect the kidney by causing vascular disease and fibrosis. Analgesics are the most commonly used drugs in the US, and chronic analgesic use may be an important, preventable cause of renal dysfunction. The primary objective of this study is to examine prospectively risk factors for renal function decline, defined as decline in estimated glomerular filtration rate (using serum creatinine) and development of microalbuminuria, among 5000 participants in two large female cohorts: the Nurses' Health Study I and the Nurses' Health Study II. Stored and newly collected blood and urine specimens will permit repeated measurements of renal function and urine albumin and will allow us to examine changes over a period of 19 years in NHS I and 11 years in NHS II. Mixed-effects regression will be used to analyze the slope of renal function in the exposed and unexposed groups during the long-term follow-up. This study will provide: 1) prospective data on risk factors for renal function decline; 2) threshold levels of safe cumulative dose of individual classes of analgesics; 3) population-based incidence rates of renal dysfunction and rate of renal function decline in younger and older women; and 4) an important resource for future long-term studies of renal function decline. [unreadable] [unreadable]